KI-67 DETECTED BY MIB-1 PREDICTS DISTANT METASTASIS AND TUMOR MORTALITY IN PRIMARY, HIGH-GRADE EXTREMITY SOFT-TISSUE SARCOMA

BACKGROUND. Preoperative staging of localized extremely soft tissue sa rcoma (STS) includes tumor grade, size, and depth. A positive microsco pic margin (PMM) adds prognostic information postoperatively, which is not helpful for preoperative stratification into low and high risk gr oups. This study was undertaken to identify molecular markers associat ed with poor outcome that could be used to refine the preoperative sta ging of high grade extremity STS. METHODS. Between January 1, 1983, an d December 31, 1989, 1416 patients were entered into the STS prospecti ve data base at the Memorial Sloan-Kettering Cancer Center. Of 232 pat ients identified with primary, high grade extremity lesions, 121 had t issue available for immunohistochemical (IHC) analysis. The clinicopat hologic variables and molecular markers for the original 232 patients were correlated with those for the 121 patients analyzed in the curren t study. Overexpression of Ki-67, p53, and mdm2 and deletion of Rb wer e determined via standard IHC techniques on serial paraffin sections. Categoric overexpression was defined as greater than or equal to 20% n uclear staining. Continuous determination of the percentage of nuclear staining was also used for correlation with distant metastasis (DM) a nd tumor mortality (TM). Univariate and multivariate analyses were con ducted with log rank and Wilcoxon tests and Cox regression analyses, r espectively. RESULTS. The median follow-up was 64 months. Fifty-four o f the 121 patients (45%) developed DM. Fifty-one of the 121 patients ( 42%) died of their disease. Factors found to be significant in univari ate and multivariate analyses for both DM and TM were Ki-67 score, siz e, and PMM (all P values <0.05). Five year freedom from DM with a Ki-6 7 score of <20 was 70% versus 50% for a score. Overexpression of p53 o f mdm2 or deletion of Rb did not correlate with increased risk of DM o r TM alone or in combination with a Ki-67 score of greater than or equ al to 20. CONCLUSIONS. In addition to standard preoperative criteria, Ki-67 score is an independent prognostic molecular marker that predict s DM and TM in high grade extremity STS. Selecting patients with high grade tumors for preoperative investigational treatment may be further refined according to whether the patients have Ki-67 score of <20 and large tumor size. Cancer 1998;83:490-7. (C) 1998 American Cancer Soci ety.